980 research outputs found

    Results from the first English stool bank using faecal microbiota transplant as a medicinal product for the treatment of Clostridioides difficile infection.

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    BACKGROUND: Faecal Microbiota Transplant (FMT) has improved outcomes for the treatment of Clostridioides difficile infection (CDI) compared to antibiotic therapy. FMT is classified as a medicinal product in the United Kingdom, similar to the USA and Canada, limiting supply via stool banks without appropriate licencing. In the largest UK cohort to date, we describe the clinical outcomes for 124 patients receiving FMT for recurrent or refractory CDI and present a framework to produce FMT as a licenced medicinal product. METHODS: Anonymous unrelated healthy donors, screened via health assessment and microbiological testing donated stool. In aerobic conditions FMT aliquots were prepared for immediate use or frozen storage, following a production framework developed to comply with Good Manufacturing Practice. Outcome measures were clinical response to FMT defined as resolution of diarrhoea within seven days and clinical cure defined as response without diarrhoea recurrence at 90 days. FINDINGS: Clinical response was 83·9% (95% CI 76·0%-90·0%) after one treatment. Clinical cure was 78·2% (95% CI 67·4%-89·0%) across the cohort. Refractory cases appeared to have a lower initial clinical response rate compared to recurrent cases, however at day 90 there were no differences observed between these groups. INTERPRETATION: The methodology developed here enabled successful licencing of FMT by The Medicines and Healthcare products Regulatory Agency as a medicinal product. This has widened the availability of FMT in the National Health Service via a stool bank and can be applied in other centres across the world to improve access to safe and quality assured treatments

    Reading Front to Back: MEG Evidence for Early Feedback Effects During Word Recognition.

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    Magnetoencephalography studies in humans have shown word-selective activity in the left inferior frontal gyrus (IFG) approximately 130 ms after word presentation (Pammer et al. 2004; Cornelissen et al. 2009; Wheat et al. 2010). The role of this early frontal response is currently not known. We tested the hypothesis that the IFG provides top-down constraints on word recognition using dynamic causal modeling of magnetoencephalography data collected, while subjects viewed written words and false font stimuli. Subject-specific dipoles in left and right occipital, ventral occipitotemporal and frontal cortices were identified using Variational Bayesian Equivalent Current Dipole source reconstruction. A connectivity analysis tested how words and false font stimuli differentially modulated activity between these regions within the first 300 ms after stimulus presentation. We found that left inferior frontal activity showed stronger sensitivity to words than false font and a stronger feedback connection onto the left ventral occipitotemporal cortex (vOT) in the first 200 ms. Subsequently, the effect of words relative to false font was observed on feedforward connections from left occipital to ventral occipitotemporal and frontal regions. These findings demonstrate that left inferior frontal activity modulates vOT in the early stages of word processing and provides a mechanistic account of top-down effects during word recognition

    Optimisation of Interface Roughness and Coating Thickness to Maximise Coating-Substrate Adhesion - A Failure Prediction and Reliability Assessment Modelling

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    This paper addresses a novel modelling technique which is based on a multidisciplinary approach to predict the coating-substrate adhesion. It proposes new equations governing coating debondment that combines material science concepts with and solid mechanics concepts. The effects of two parameters i.e. interface roughness λ and coating thickness h on coating-substrate adhesion has been analysed. The reliability of newly developed technique has been validated by comparison with the experimental results

    Phonon-assisted radiofrequency absorption by gold nanoparticles resulting in hyperthermia

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    It is suggested that in gold nanoparticles (GNPs) of about 5 nm sizes used in the radiofrequency (RF) hyperthermia, an absorption of the RF photon by the Fermi electron occurs with involvement of the longitudinal acoustic vibrational mode (LAVM), the dominating one in the distribution of vibrational density of states (VDOS). This physical mechanism helps to explain two observed phenomena: the size dependence of the heating rate (HR) in GNPs and reduced heat production in aggregated GNPs. The argumentation proceeds within the one-electron approximation, taking into account the discretenesses of energies and momenta of both electrons and LAVMs. The heating of GNPs is thought to consist of two consecutive processes: first, the Fermi electron absorbs simultaneously the RF photon and the LAVM available in the GNP; hereafter the excited electron gets relaxed within the GNP's boundary, exciting a LAVM with the energy higher than that of the previously absorbed LAVM. GNPs containing the Ta and/or Fe impurities are proposed for the RF hyperthermia as promising heaters with enhanced HRs, and GNPs with rare-earth impurity atoms are also brought into consideration. It is shown why the maximum HR values should be expected in GNPs with about 5-7 nm size.Comment: proceedings at the NATO Advanced Research workshop FANEM-2015 (Minsk, May 25-27, 2015). To be published in the final form in: "Fundamental and Applied NanoElectroMagnetics" (Springer Science + Business Media B.V.

    Plan de negocios para la implementaci?n de un hotel boutique de tres estrellas, ubicado en el centro hist?rico de Cusco

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    La propuesta del presente plan de negocios es determinar la viabilidad econ?mica y financiera del formato de hotel boutique de tres estrellas, denominado Saphi Inn Hotel Boutique, se utilizaron herramientas de investigaci?n metodol?gicas en la recolecci?n de datos e informaci?n de las fuentes primarias a trav?s de entrevistas a profundidad a voceros y portavoces pertenecientes a organismos p?blicos y privados m?s relevantes del rubro hotelero, los aportes y observaciones ofrecidas permitieron desarrollar el dise?o de encuestas destinadas al principal segmento objetivo de turistas en la ciudad del Cusco, la investigaci?n de fuentes secundarias se realiz? en la b?squeda de informaci?n oficialmente publicada de organizaciones nacionales como MINCETUR y organizaciones internacionales autorizadas en el rubro. Los an?lisis de resultados permitieron elaborar el dise?o del proyecto con la visi?n de incentivar la mejora de la calidad de los servicios hoteleros y tur?sticos basados en una propuesta atractiva dirigida al p?blico objetivo principal del entorno internacional, y la rentabilidad del concepto en beneficio de los accionistas, propietarios y la comunidad para obtener como resultado esperado, el crecimiento del flujo de turistas que visitan el pa?s, con la ciudad del Cusco como protagonista, el cual es brinda como pron?stico de resultado la futura rentabilidad de nuevos hoteles en la proyecci?n de crecimiento para el a?o 2020, donde se estima 4 millones de turistas, un 35% por encima de las cifras actuales, el total de datos cuantitativos recolectados fueron de 384 encuestas, dirigidas a turismo receptivo, las cuales fueron realizadas en el centro de la ciudad del Cusco, 301 encuestas se realizaron de forma presencial, otras 83 encuestas a trav?s de internet. Como recomendaci?n se propone la activaci?n del plan de negocio en el sustento de una oportunidad de demanda de una necesidad aun insatisfecha

    Demographic parameters of reintroduced grey partridges in central Italy and the effect of weather

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    International audienceGrey partridge populations declined in Europe from mid-1950s onwards mostly due to modifications of agricultural cropping. In Italy, the decline was even more dramatic because of over-hunting and restocking with allochthonous birds. We carried out a research on a re-introduced population in Central Italy from 1995 to 2005, with the aim of evaluating the reintroduction success and separating the intrinsic and external factors influencing year-to-year changes in partridge density with particular respect to the weather. Average spring density was 4.5 pairs per square kilometre (SD = 1.52); our population reached a peak few years after the reintroduction and then declined. Brood production rate was close to that of declining European populations (average 33.9%; SD = 10.21), and chick survival rate (average 40%; = 17.61) determined the change of breeding abundance from year to year + 1. Our population seemed to be mainly affected by brood production and chick survival rates and by the weather; in particular, higher early winter and spring temperatures increased breeding density whilst higher early summer temperatures decreased brood production rate

    Developing a matrix to identify and prioritise research recommendations in HIV Prevention

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    BACKGROUND: HIV prevention continues to be problematic in the UK, as it does globally. The UK Department of Health has a strategic direction with greater focus on prevention as part of its World Class Commissioning Programme. There is a need for targeted evidence-based prevention initiatives. This is an exploratory study to develop an evidence mapping tool in the form of a matrix: this will be used to identify important gaps in contemporary HIV prevention evidence relevant to the UK. It has the potential to aid prioritisation in future research.METHODS: Categories for prevention and risk groups were developed for HIV prevention in consultation with external experts. These were used as axes on a matrix tool to map evidence. Systematic searches for publications on HIV prevention were undertaken using electronic databases for primary and secondary research undertaken mainly in UK, USA, Canada, Australia and New Zealand, 2006-9. Each publication was screened for inclusion then coded. The risk groups and prevention areas in each paper were counted: several publications addressed multiple risk groups. The counts were exported to the matrix and clearly illustrate the concentrations and gaps of literature in HIV prevention.RESULTS: 716 systematic reviews, randomised control trials and other primary research met the inclusion criteria for HIV prevention. The matrix identified several under researched areas in HIV prevention.CONCLUSIONS: This is the first categorisation system for HIV prevention and the matrix is a novel tool for evidence mapping. Some important yet under-researched areas have been identified in HIV prevention evidence: identifying the undiagnosed population; international adaptation; education; intervention combinations; transgender; sex-workers; heterosexuals and older age groups.<br/

    Cancer incidence patterns by region and socioeconomic deprivation in teenagers and young adults in England

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    Data on 35 291 individuals with cancer, aged 13–24 years, in England from 1979 to 2001 were analysed by region and socio-economic deprivation of census ward of residence, as measured by the Townsend deprivation index. The incidence of leukaemia, lymphoma, central nervous system tumours, soft tissue sarcomas, gonadal germ cell tumours, melanoma and carcinomas varied by region (P<0.01, all groups) but bone tumour incidence did not. Lymphomas, central nervous system tumours and gonadal germ cell tumours all had higher incidence in less deprived census wards (P<0.01), while chronic myeloid leukaemia and carcinoma of the cervix had higher incidence in more deprived wards (P<0.01). In the least deprived wards, melanoma incidence was nearly twice that in the most deprived, but this trend varied between regions (P<0.001). These cancer incidence patterns differ from those seen in both children and older adults and have implications for aetiology and prevention
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